Randomized Phase II Trial of First-Line Treatment With Sorafenib Versus Interferon Alfa-2a in Patients With Metastatic Renal Cell Carcinoma

Escudier, Bernard; Szczylik, Cezary; Hutson, Thomas E.; Demkow, Tomasz; Staehler, Michael; Rolland, Frédéric; Négrier, Sylvie; Laferriere, Nicole; Scheuring, Urban; Cella, David; Shah, Sundeep; Bukowski, Ronald M.

doi:10.1200/jco.2008.19.3342

Cited by 450 publications

(339 citation statements)

References 22 publications

Supporting

Mentioning

316

Contrasting

Unclassified

Order By: Relevance

“…Accordingly, given the interindividual variability of the values of the sorafenib area under the plasma concentration-time curve over 12 hours (AUC), the lack of effect observed in patients with 0.2 AOPP may be linked to an underexposure (40). To date, the bulk of data on dose exposure to sorafenib is growing and suggests a potential benefit for sorafenib dose-escalation strategies in renal cell carcinoma (41). Considering those results and the sorafenib pharmacokinetic analysis, the assay of serum AOPP might become a useful and early indicator of sorafenib effectiveness.…”

Section: Discussionmentioning

confidence: 99%

Sorafenib-Induced Hepatocellular Carcinoma Cell Death Depends on Reactive Oxygen Species ProductionIn VitroandIn Vivo

Coriat

Nicco

Chéreau

et al. 2012

Molecular Cancer Therapeutics

184

145

View full text Add to dashboard Cite

Sorafenib is presently the only effective therapy in advanced hepatocellular carcinoma (HCC). Because most anticancer drugs act, at least in part, through the generation of reactive oxygen species, we investigated whether sorafenib can induce an oxidative stress. The effects of sorafenib on intracellular ROS production and cell death were assessed in vitro in human (HepG2) and murine (Hepa 1.6) HCC cell lines and human endothelial cells (HUVEC) as controls. In addition, 26 sera from HCC patients treated by sorafenib were analyzed for serum levels of advanced oxidation protein products (AOPP). Sorafenib significantly and dosedependently enhanced in vitro ROS production by HCC cells. The SOD mimic MnTBAP decreased sorafenibinduced lysis of HepG2 cells by 20% and of Hepa 1.6 cells by 75% compared with HCC cells treated with 5 mg/L sorafenib alone. MnTBAP significantly enhanced by 25% tumor growth in mice treated by sorafenib. On the other hand, serum levels of AOPP were higher in HCC patients treated by sorafenib than in sera collected before treatment (P < 0.001). An increase in serum AOPP concentration !0.2 mmol/L chloramine T equivalent after 15 days of treatment is a predictive factor for sorafenib response with higher progression free survival (P < 0.05) and overall survival rates (P < 0.05). As a conclusion, sorafenib dose-dependently induces the generation of ROS in tumor cells in vitro and in vivo. The sera of Sorafenib-treated HCC patients contain increased AOPP levels that are correlated with the clinical effectiveness of sorafenib and can be used as a marker of effectiveness of the drug.

show abstract

Section: Discussionmentioning

confidence: 99%

Sorafenib-Induced Hepatocellular Carcinoma Cell Death Depends on Reactive Oxygen Species ProductionIn VitroandIn Vivo

Coriat

Nicco

Chéreau

et al. 2012

Molecular Cancer Therapeutics

184

145

View full text Add to dashboard Cite

show abstract

“…For Switzerland we see a rapid uptake, and then a decline, which may be dependent on substitution with sunitinib or other drugs. The low use of sorafenib in the US may be related to the fact that sunitinib was available first, and that phase II study data for sorafenib at launch did not show an increase in PFS with sorafenib compared with IFNa (5.7 versus 5.6 months) when used first-line, making its role in therapy of untreated patients unclear [10] (Fig. 4).…”

Section: Uptake and Use Of New Drugs For Mrccmentioning

confidence: 99%

Cost effectiveness in practice and its effect on clinical outcomes

Ramsey

Wilking

2014

Journal of Cancer Policy

View full text Add to dashboard Cite

a b s t r a c tThe value of new cancer drugs is maximized when they are used for the right patient in the right way in clinical practice. Clinical trials conducted during drug development are the most important source of information to predict value at the time a drug is introduced in practice. Regulatory approval is an indication of value, which lately has been complemented with an assessment of clinical value for decisions about reimbursement, using the methodology of health technology assessment (HTA). Formal cost-effectiveness studies are an important part of this methodology, aiming to assist decisions about value for money in health care spending. The question is if the addition of a complementary HTA and cost-effectiveness study increases the value realized by the drug in practice compared to how it would be used without these assessments.We review the issues involved in providing an answer by using the introduction of new targeted therapies for metastatic renal cell cancer (mRCC). Specifically, we examine the link between clinical trial data and estimations of cost-effectiveness at drug launch, reimbursement decisions, uptake and use in different countries and evidence about impact on outcome in patient populations for which the new drugs are indicated.We conclude that there is a weak link between the assessments used at drug launch and the value created in clinical practice. We suggest measures that are necessary for the achievement of evidencebased and cost-effective cancer care in clinical practice.

show abstract

“…[10][11][12] As initial treatment with cytokines has become significantly less common in mRCC, and in light of data failing to demonstrate a progression-free survival (PFS) benefit of sorafenib over interferon in the front-line setting, 12 sorafenib is often used in the second-line setting after prior VEGF-targeted treatment. This practice algorithm is common, although it has not been prospectively investigated.…”

mentioning

confidence: 99%

Sorafenib in patients with metastatic renal cell carcinoma refractory to either sunitinib or bevacizumab

García

Hutson

Elson

et al. 2010

Cancer

Self Cite

View full text Add to dashboard Cite

BACKGROUND: Bevacizumab and sunitinib are standard initial therapy in metastatic renal cell carcinoma (mRCC). Despite common use, the safety and activity of sorafenib in bevacizumab-or sunitinib-refractory mRCC have not been prospectively investigated. METHODS: Metastatic RCC patients with Response Evaluation Criteria in Solid Tumors (RECIST)-defined disease progression (PD) after treatment with either bevacizumab or sunitinib received twice daily 400 mg of sorafenib in a multicenter, prospective phase 2 study. Dose escalation was permitted in the absence of significant toxicity. The primary endpoint was tumor burden reduction rate, defined as the proportion of patients with !5% reduction in the sum of RECIST-defined target lesions without other PD. Secondary endpoints included progression-free survival (PFS), duration of response, overall survival, and safety. A 2-stage accrual design was used to test the alternative hypothesis that the tumor burden reduction rate was >20% versus <5%. RESULTS: Forty-eight patients were enrolled. The tumor burden reduction rate was 30% (95% confidence interval [CI], 17%-45%). One unconfirmed objective partial response was observed. The median PFS was 4.4 months (95% CI, 3.6-5.9). There was no association of PFS and tumor shrinkage with response to prior therapy. Most treatment-related adverse events were of mild-to-moderate intensity, and included fatigue, hypertension, diarrhea, and palmoplantar erythrodysesthesia (PPE). Patients previously treated with bevacizumab tended to develop more PPE (P ¼ .03) and mucositis (P ¼ .06), whereas sunitinib-treated patients tended to develop more skin rash (P ¼ .06). CONCLUSIONS: Administration of sorafenib is safe and feasible in patients with mRCC refractory to either bevacizumab or sunitinib. Modest clinical activity was observed supporting current practice patterns of sequential vascular endothelial growth factor-targeted therapy in mRCC. Cancer 2010;116:5383-90.

show abstract

Randomized Phase II Trial of First-Line Treatment With Sorafenib Versus Interferon Alfa-2a in Patients With Metastatic Renal Cell Carcinoma

Cited by 450 publications

References 22 publications

Sorafenib-Induced Hepatocellular Carcinoma Cell Death Depends on Reactive Oxygen Species ProductionIn VitroandIn Vivo

Sorafenib-Induced Hepatocellular Carcinoma Cell Death Depends on Reactive Oxygen Species ProductionIn VitroandIn Vivo

Cost effectiveness in practice and its effect on clinical outcomes

Sorafenib in patients with metastatic renal cell carcinoma refractory to either sunitinib or bevacizumab

Contact Info

Product

Resources

About